ADPKD is a chronic and progressive genetic disease that causes the proliferation and growth of cysts in the kidneys. Existing drugs only treat the signs and symptoms of ADPKD (kidney cysts, pain and hypertension).
Tolvaptan is a selective vasopressin V2-receptor antagonist that slows cyst growth and renal function decline. It is administered in a twice-daily split-dose regimen, with the morning dose taken at least 30 minutes before food.
Safety and efficacy of tolvaptan were assessed in a multicentre, double-blind, phase III trial (n=1445). Patients with evidence of rapidly progressing early ADPKD (total kidney volume ≥750ml, estimated CrCl ≥60ml/min) were randomised to receive placebo or the highest tolerable of three twice-daily regimens of tolvaptan.
Over the 3-year study period, the rate of total kidney volume increase in the tolvaptan group was 2.8% per year (95% CI 2.5—3.1) compared with 5.5% per year in the placebo group (95% CI 5.1—6.0; p<0.001). Tolvaptan was associated with a significant reduction in the risk of multiple events of worsening renal function, pain, hypertension or albuminuria (HR 0.87, 95% CI 0.78—0.97; p=0.0095).
The most commonly reported adverse effects of tolvaptan were thirst, polyuria, nocturia and pollakiuria.
Clinically significant liver enzyme elevations were more common with tolvaptan than placebo (4.9% vs 1.2%). No cases of hepatic failure were reported; however, additional monitoring is recommended to mitigate the potential risk of irreversible liver injury. Prescribers should monitor patients' liver function before starting treatment with tolvaptan, and monthly for the first 18 months and every three months thereafter.
The safety and efficacy of tolvaptan in CKD stage 5 has not been adequately studied; therefore treatment should be discontinued if renal insufficiency progresses to CKD stage 5.